Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism

In what is being described as cutting-edge research, published in the Journal of Immunology, scientists from the University of Virginia School of Medicine suggest that a mother’s microbiome during pregnancy plays a critical role in determining the child’s risk of developing autism-spectrum disorders. The study raises the possibility that autism prevention might involve modifying an expectant mom’s diet or taking custom probiotics. The researchers were actually able to prevent the development of autism-like neurodevelopmental disorders in lab mice.

“We determined that the microbiome is a key contributor in determining susceptibility [to autism-like disorders], so it suggests that you could target either the maternal microbiome or this inflammatory molecule, IL-17a,” said lead researcher John Lukens, PhD, of UVA’s Department of Neuroscience. “You could also use this [IL-17a] as a biomarker for early diagnosis.”

Microbiome and Autism

This groundbreaking work from Lukens and his colleagues ads to further evidence of the complexity involving the relationship between the health of the mother’s microbiome and healthy development of her children. “The microbiome can shape the developing brain in multiple ways,” explained Lukens, of UVA’s Center for Brain Immunology and Glia (BIG) and UVA’s Carter Immunology Center. “The microbiome is really important to the calibration of how the offspring’s immune system is going to respond to an infection or injury or stress.”

But an unhealthy microbiome in the mom can create problems: Lukens’ work shows that it can make her unborn offspring susceptible to neurodevelopmental disorders. The researchers found that the IL-17a molecule was a key contributor to the development of autism-like symptoms in lab mice.

The good news: The microbiome can be modified easily, either through diet, probiotic supplements or fecal transplant. All of these approaches seek to restore a healthy equilibrium among the different microorganisms that live in the gut.

“In terms of translating our work to humans, I think the next big step would be to identify features of the microbiome in pregnant mothers that correlate with autism risk,” Lukens said. “I think the really important thing is to figure out what kind of things can be used to modulate the microbiome in the mother as effectively and safely as we can.”

Another Option for Preventing Autism

Blocking IL-17a also might offer a way to prevent autism, but Lukens said that path carries much more risk. “If you think about pregnancy, the body is basically accepting foreign tissue, which is a baby,” he said. “As a result, maintenance of embryonic health demands a complex balance of immune regulation, so people tend to shy away from manipulating the immune system during pregnancy.”

IL-17a previously has been implicated in conditions such as rheumatoid arthritis, multiple sclerosis and psoriasis, and there are already drugs available that target it. But Lukens noted that the molecule has an important purpose in stopping infections, especially fungal infections. Blocking it, he said, “could make you susceptible to all kinds of infections.” And doing so during pregnancy could have complex ripple effects on a child’s development that scientists would need to sort out.

For their next steps, Lukens and his team plan to explore the potential role of other immune molecules in the development of autism and other such conditions. IL-17a may be just one piece in a much larger puzzle, he said.

While Lukens’ work links the immune system with neurodevelopmental disorders, he emphasized that this in no way suggests that vaccines are contributing to the development of autism. “There’s a definite link between the immune response and the developing brain,” he said. “It just doesn’t have anything to do with vaccines. It’s much, much earlier.”